The overall goal of this project is to increase our basic knowledge about the biology of cell replication in human neuroblastoma. Two models will be studied: the first consists of several human neuroblastoma lines in vitro and the second consists of these neuroblastoma lines grown in solid tumor form in the immunodeficient nude mouse. These tumors will be examined for synchrony, diurnal variations, and changes in proliferative characteristics with increasing size. The classic cell kinetics measurements, such a labelling and mitotic indices, and fraction-labelled mitoses curves, will be performed to determine baseline cell cycle times and parameters. Several newer techniques will be used also. First, flow cytofluorometry will be used to study overall changes in DNA distributions wthin the tumors. Combined tritiated thymidine autoradiography and DNA cytofluorometry will be used to provide independent measurements of DNA synthesis status and cell cycle position to study the kinetic characteristics of proliferating and non-proliferating cells. These studies will provide a detailed analysis of the cell kinetics of untreated neuroblastoma in order to provide a baseline with which treatment can be rationally formulated and against which therapeutic efforts can be objectively compared.